Gemcitabine Doxorubicin

The NCCN guidelines recommend retreatment with either paclitaxel or platinum, or the combination of paclitaxel and a platinum compound if disease recurs more than 6 months after the initial treatment with paclitaxel in combination with a platinum analog. Treatment options for patients with refractory disease or disease recurrence within 6 months after treatment include topotecan, altretamine, oral etopo-side, liposomal doxorubicin, gemcitabine, tamoxifen, referral for a clinical trial, or supportive care therapy. 

More recently, a German study compared a dose-escalated regimen of BEACOPP (with filgrastim support) with standard-dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone, gemcitabine (BEACOPP) and COPP alternating with ABVD (C—cyclophosphamide instead of mechlorethamine for MOPP).18 The escalated BEACOPP was... 

Combination studies of olaparib are being explored clinically with a number of agents, including irinotecan, dacarbazine, carboplatin, gemcitabine, doxorubicin, cisplatin, and topotecan. 

Recurrent SCLC is usually less sensitive to chemotherapy. If recurrence is more than 6 months after induction chemotherapy, the original regimen can be repeated. If recurrence occurs in less than 6 months but >3 months, treatment options include a taxane, gemcitabine, topotecan, irinotecan, CAV (cyclophosphamide, doxorubicin, and vincristine), and vinorelbine. 

Chemotherapeutic agents that have significant cancer response when combined with hyperthermia (up to 43°C) include doxorubicin, melphalan, mitomycin C (MMC), mitoxantrone, gemcitabine, etoposide, and especially the platinum-based agents carboplatin and oxaliplatin (Mohamed et al., 2003 Sugarbaker et al., 2005). Agents that do not work well with hyperthermia include irinotecan, paclitaxel, docetaxel, 5-fluorouracil, and floxuridine (Mohamed et al., 2003 Sugarbaker et al., 2005). 

In 10 studies the corresponding clinical study protocol stipulated that cetuximab was to be given in combination with a chemotherapeutic agent (irinotecan, paclitaxel, gemcitabine, cisplatin, carboplatin, or doxorubicin) or in combination with radiation therapy. 

The possible impact of co-administered chemotherapies and radiation therapy on the PK of cetuximab was furthermore assessed using the population PK approach, as described in Section 14.6. The co-administered chemotherapies included cisplatin, carboplatin, paclitaxel, doxorubicin, irinotecan, and gemcitabine. The results of the analysis indicate that neither the co-administered chemotherapies nor radiation therapy had a significant impact on the PK of cetuximab. This finding suggests that the potential for PK-based drug-drug interactions with cetuximab is low. 

Radiation recall consists of inflammatory reactions triggered by cytotoxic drugs in previously irradiated areas most are skin reactions. Gemcitabine has been implicated in several cases. The authors of a literature review discovered 12 cases of radiation recall caused by gemcitabine and reported a case of myositis in the rectus abdominis muscle of a patient with pancreatic adenocarcinoma as an effect of radiation recall (23). Most of the cases had inflammation of internal organs or tissues and 30% had dermatitis or mucositis. This is different from the effect of other agents that commonly cause radiation recall (anthracyclines and taxanes), with which 63% are skin reactions. Compared with anthracyclines and taxanes, the interval from the completion of radiation therapy to the start of chemotherapy is less with gemcitabine (median time 56 days, compared with 218 days for the taxanes and 646 days for doxorubicin). 

Clinically important, potentially hazardous interactions with altretamine, amikacin, aminoglycosides, antineoplastics, bleomycin, busulfan, carboplatin, carmustine, chlorambucil, cisplatin, corticosteroids, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daunorubicin, docetaxel, doxorubicin, estramustine, etoposide, fludarabine, fluorouracil, gemcitabine, gentamicin, hydroxyurea, idarubicin, ifosfamide, indomethacin, kanamycin, levamisole, lomustine, mechlorethamine, melphalan, mercaptopurine, methotrexate, mitomycin, mitotane, mitoxantrone, neomycin, pentostatin, plicamycin, procarbazine, streptomycin, streptozocin, thioguanine, thiotepa, tobramycin, tretinoin, uracil, vinblastine, vincristine, vinorelbine... 

Docetaxel and prednisone have recently been shown to improve survival in hormone-refractory metastatic prostate cancer and should be considered standard therapy. Single agents with modest activity in prostate cancer include cyclophosphamide, estramustine, 5-fluorouracil, methotrexate, dacarbazine, mitoxantrone, doxorubicin, pachtaxel, gemcitabine, vinorelbine, and cisplatin. If disease stabilization is included as a favorable response, response rates np to 46% have been reported. Several trials have evalnated the varions combination regimens containing the most active single agents. ... 

Joyce, a psychologist. Ovarian cancer, stage 3, diagnosed in 2004 at age fifty-eight. (Treatment surgery, hysterectomy, splenectomy, and colon resection. Chemo carboplatin, paclitaxel, cisplatin, gemcitabine, topotecan, doxorubicin.)... 

Maria. Employed in sales. Breast cancer, diagnosed in 2005 at age thirty-two. (Treatment bilateral mastectomies, radiation. Chemo Four rounds of doxorubicin and cyclophosphamide four rounds of paclitaxel four rounds of gemcitabine with cisplatin.)... 

A number of case reports describe an increase in the effects of warfarin, accompanied by bleeding in some cases, caused by an-tineoplastic regimens containing carboplatin, chlormethine, cyclophosphamide, doxorubicin, etoposide, gefitinib, gemcitabine, ifosfamide with mesna, methotrexate, procarbazine, trastuzum-ab, vincristine or vindesine. A decrease in the effects of warfarin has been seen with azathioprine, cyclophosphamide, mercaptop-urine and mitotane, a decrease in the effects of acenocoumarol has been seen with mercaptopurine, and a decrease in the effects of phenprocoumon have l n seen with azathioprine. 

The concurrent use of gemcitabine and doxorubicin or epirubicin does not appear to affect the pharmacokinetics of either drug. An in vitro study found that the efficacy of the combination of gemcitabine and epirubicin may be schedule-dependent. 

The pharmacokinetics of gemcitabine and doxorubicin did not differ when they were given on the same day, when compared with when they were given alone in patients with breast cancer. Similarly, gemcitabine pharmacokinetics were unchanged by the concurrent use of epirubicin and paclitaxel in patients with breast cancer, and gemcitabine did not alter the interaction between epirubicin and paclitaxel (see Anthracyclines -i-Taxanes , p.612). 

Jacquin JP, Chargari C, Thorin J, MiUe D, MeUs A, Orfeuvre H, et al. Phase II trial of pegylated liposomal doxorubicin in combination with gemcitabine in metastatic breast cancer patients. Am J Clin Oncol 2012 35(1) 18-21. 

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